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• W4323657859 abstract "Antibiotic administration during early life has been shown to have lasting effects on the gut microbiota, which have been linked to sustained alterations in liver metabolism and adiposity. Recent investigations have discerned that the gut microbiota continues to develop toward an adult-like profile during adolescence. However, the impact of antibiotic exposure during adolescence on metabolism and adiposity is unclear. Herein, a retrospective analysis of Medicaid claims data was performed, which indicated that tetracycline class antibiotics are commonly prescribed for the systemic treatment of adolescent acne. The purpose of this was to discern the impact of a prolonged tetracycline antibiotic exposure during adolescence on the gut microbiota, liver metabolism, and adiposity. Male C57BL/6T specific pathogen-free mice were administered a tetracycline antibiotic during the pubertal/postpubertal adolescent growth phase. Groups were euthanized at different time points to assess immediate and sustained antibiotic treatment effects. Antibiotic exposure during adolescence caused lasting genera-level shifts in the intestinal bacteriome and persistent dysregulation of metabolic pathways in the liver. Dysregulated hepatic metabolism was linked to sustained disruption of the intestinal farnesoid X receptor–fibroblast growth factor 15 axis, a gut-liver endocrine axis that supports metabolic homeostasis. Antibiotic exposure during adolescence increased subcutaneous, visceral, and marrow adiposity, which intriguingly manifested following antibiotic therapy. This preclinical work highlights that prolonged antibiotic courses for the clinical treatment of adolescent acne may have unintended deleterious effects on liver metabolism and adiposity. Antibiotic administration during early life has been shown to have lasting effects on the gut microbiota, which have been linked to sustained alterations in liver metabolism and adiposity. Recent investigations have discerned that the gut microbiota continues to develop toward an adult-like profile during adolescence. However, the impact of antibiotic exposure during adolescence on metabolism and adiposity is unclear. Herein, a retrospective analysis of Medicaid claims data was performed, which indicated that tetracycline class antibiotics are commonly prescribed for the systemic treatment of adolescent acne. The purpose of this was to discern the impact of a prolonged tetracycline antibiotic exposure during adolescence on the gut microbiota, liver metabolism, and adiposity. Male C57BL/6T specific pathogen-free mice were administered a tetracycline antibiotic during the pubertal/postpubertal adolescent growth phase. Groups were euthanized at different time points to assess immediate and sustained antibiotic treatment effects. Antibiotic exposure during adolescence caused lasting genera-level shifts in the intestinal bacteriome and persistent dysregulation of metabolic pathways in the liver. Dysregulated hepatic metabolism was linked to sustained disruption of the intestinal farnesoid X receptor–fibroblast growth factor 15 axis, a gut-liver endocrine axis that supports metabolic homeostasis. Antibiotic exposure during adolescence increased subcutaneous, visceral, and marrow adiposity, which intriguingly manifested following antibiotic therapy. This preclinical work highlights that prolonged antibiotic courses for the clinical treatment of adolescent acne may have unintended deleterious effects on liver metabolism and adiposity. The gut microbiota, which is the community of microorganisms colonizing the gut, interacts with the host to influence host immunity and metabolism.1Sommer F. Backhed F. The gut microbiota--masters of host development and physiology.Nat Rev Microbiol. 2013; 11: 227-238Google Scholar, 2Schroeder B.O. Bäckhed F. Signals from the gut microbiota to distant organs in physiology and disease.Nat Med. 2016; 22: 1079-1089Google Scholar, 3Krautkramer K.A. Fan J. Bäckhed F. Gut microbial metabolites as multi-kingdom intermediates.Nat Rev Microbiol. 2021; 19: 77-94Google Scholar, 4Fan Y. Pedersen O. Gut microbiota in human metabolic health and disease.Nat Rev Microbiol. 2021; 19: 55-71Google Scholar Prior studies have demonstrated that the gut microbiota critically regulates hepatic metabolism and host adiposity.5Bäckhed F. Ding H. Wang T. Hooper L.V. Koh G.Y. Nagy A. Semenkovich C.F. Gordon J.I. The gut microbiota as an environmental factor that regulates fat storage.Proc Natl Acad Sci U S A. 2004; 101: 15718-15723Google Scholar, 6Turnbaugh P.J. Bäckhed F. Fulton L. Gordon J.I. Diet-induced obesity is linked to marked but reversible alterations in the mouse distal gut microbiome.Cell Host Microbe. 2008; 3: 213-223Google Scholar, 7Turnbaugh P.J. Ley R.E. Mahowald M.A. Magrini V. Mardis E.R. Gordon J.I. An obesity-associated gut microbiome with increased capacity for energy harvest.Nature. 2006; 444: 1027-1031Google Scholar Gnotobiotic animal studies have shown that germ-free mice are leaner than conventionally raised mice.5Bäckhed F. Ding H. Wang T. Hooper L.V. Koh G.Y. Nagy A. Semenkovich C.F. Gordon J.I. The gut microbiota as an environmental factor that regulates fat storage.Proc Natl Acad Sci U S A. 2004; 101: 15718-15723Google Scholar Transplanting the gut microbiota from conventionally raised mice to germ-free mice caused an up-regulation of hepatic de novo lipogenesis and increased body fat mass.5Bäckhed F. Ding H. Wang T. Hooper L.V. Koh G.Y. Nagy A. Semenkovich C.F. Gordon J.I. The gut microbiota as an environmental factor that regulates fat storage.Proc Natl Acad Sci U S A. 2004; 101: 15718-15723Google Scholar Furthermore, transplanting the gut microbiota of conventionally raised obese mice to germ-free mice led to a more significant increase in adiposity than transplantation from conventionally raised lean mice.6Turnbaugh P.J. Bäckhed F. Fulton L. Gordon J.I. Diet-induced obesity is linked to marked but reversible alterations in the mouse distal gut microbiome.Cell Host Microbe. 2008; 3: 213-223Google Scholar,7Turnbaugh P.J. Ley R.E. Mahowald M.A. Magrini V. Mardis E.R. Gordon J.I. An obesity-associated gut microbiome with increased capacity for energy harvest.Nature. 2006; 444: 1027-1031Google Scholar These investigations support the premise that the composition of the gut microbiota plays a role in regulating liver metabolism and host adiposity. Antibiotic administration during critical phases of development and long-term treatment courses impair the gut microbiota's ability to recover to a stable state.8Ianiro G. Tilg H. Gasbarrini A. Antibiotics as deep modulators of gut microbiota: between good and evil.Gut. 2016; 65: 1906-1915Google Scholar, 9Becattini S. Taur Y. Pamer E.G. Antibiotic-induced changes in the intestinal microbiota and disease.Trends Mol Med. 2016; 22: 458-478Google Scholar, 10Sommer F. Anderson J.M. Bharti R. Raes J. Rosenstiel P. The resilience of the intestinal microbiota influences health and disease.Nat Rev Microbiol. 2017; 15: 630-638Google Scholar, 11Fassarella M. Blaak E.E. Penders J. Nauta A. Smidt H. Zoetendal E.G. Gut microbiome stability and resilience: elucidating the response to perturbations in order to modulate gut health.Gut. 2021; 70: 595-605Google Scholar Antibiotic-induced dysbiotic changes in the indigenous gut microbiota can have detrimental effects on host metabolism.4Fan Y. Pedersen O. Gut microbiota in human metabolic health and disease.Nat Rev Microbiol. 2021; 19: 55-71Google Scholar,8Ianiro G. Tilg H. Gasbarrini A. Antibiotics as deep modulators of gut microbiota: between good and evil.Gut. 2016; 65: 1906-1915Google Scholar, 9Becattini S. Taur Y. Pamer E.G. Antibiotic-induced changes in the intestinal microbiota and disease.Trends Mol Med. 2016; 22: 458-478Google Scholar, 10Sommer F. Anderson J.M. Bharti R. Raes J. Rosenstiel P. The resilience of the intestinal microbiota influences health and disease.Nat Rev Microbiol. 2017; 15: 630-638Google Scholar, 11Fassarella M. Blaak E.E. Penders J. Nauta A. Smidt H. Zoetendal E.G. Gut microbiome stability and resilience: elucidating the response to perturbations in order to modulate gut health.Gut. 2021; 70: 595-605Google Scholar Previously studies have demonstrated that antibiotic exposure during early murine postnatal development has lasting effects on hepatic metabolism and host adiposity.12Cho I. Yamanishi S. Cox L. Methé B.A. Zavadil J. Li K. Gao Z. Mahana D. Raju K. Teitler I. Li H. Alekseyenko A.V. Blaser M.J. Antibiotics in early life alter the murine colonic microbiome and adiposity.Nature. 2012; 488: 621-626Google Scholar,13Cox L.M. Yamanishi S. Sohn J. Alekseyenko A.V. Leung J.M. Cho I. Kim S.G. Li H. Gao Z. Mahana D. Zárate Rodriguez J.G. Rogers A.B. Robine N. Loke P. Blaser M.J. Altering the intestinal microbiota during a critical developmental window has lasting metabolic consequences.Cell. 2014; 158: 705-721Google Scholar Furthermore, clinical investigations have revealed that antibiotic treatments within the first 3 years of life increase the risk of higher central adiposity and obesity later in childhood.14Ajslev T.A. Andersen C.S. Gamborg M. Sørensen T.I. Jess T. Childhood overweight after establishment of the gut microbiota: the role of delivery mode, pre-pregnancy weight and early administration of antibiotics.Int J Obes (Lond). 2011; 35: 522-529Google Scholar, 15Azad M.B. Bridgman S.L. Becker A.B. Kozyrskyj A.L. Infant antibiotic exposure and the development of childhood overweight and central adiposity.Int J Obes (Lond). 2014; 38: 1290-1298Google Scholar, 16Bailey L.C. Forrest C.B. Zhang P. Richards T.M. Livshits A. DeRusso P.A. Association of antibiotics in infancy with early childhood obesity.JAMA Pediatr. 2014; 168: 1063-1069Google Scholar, 17Vallianou N. Dalamaga M. Stratigou T. Karampela I. Tsigalou C. Do antibiotics cause obesity through long-term alterations in the gut microbiome? a review of current evidence.Curr Obes Rep. 2021; 10: 244-262Google Scholar Early studies proposed that the gut microbiota reaches a stable, adult-like state within the first 3 years of life.18Koenig J.E. Spor A. Scalfone N. Fricker A.D. Stombaugh J. Knight R. Angenent L.T. Ley R.E. Succession of microbial consortia in the developing infant gut microbiome.Proc Natl Acad Sci. 2011; 108: 4578-4585Google Scholar,19Yatsunenko T. Rey F.E. Manary M.J. Trehan I. Dominguez-Bello M.G. Contreras M. Magris M. Hidalgo G. Baldassano R.N. Anokhin A.P. Heath A.C. Warner B. Reeder J. Kuczynski J. Caporaso J.G. Lozupone C.A. Lauber C. Clemente J.C. Knights D. Knight R. Gordon J.I. Human gut microbiome viewed across age and geography.Nature. 2012; 486: 222-227Google Scholar However, recent reports support that adolescence, which encompasses the pubertal/postpubertal growth phase, is a critical developmental period during which the gut microbiota continues to progress toward an adult-like profile.20Moran-Ramos S. Lopez-Contreras B.E. Villarruel-Vazquez R. Ocampo-Medina E. Macias-Kauffer L. Martinez-Medina J.N. Villamil-Ramirez H. León-Mimila P. Del Rio-Navarro B.E. Ibarra-Gonzalez I. Vela-Amieva M. Gomez-Perez F.J. Velazquez-Cruz R. Salmeron J. Reyes-Castillo Z. Aguilar-Salinas C. Canizales-Quinteros S. Environmental and intrinsic factors shaping gut microbiota composition and diversity and its relation to metabolic health in children and early adolescents: a population-based study.Gut Microbes. 2020; 11: 900-917Google Scholar,21Korpela K. Kallio S. Salonen A. Hero M. Kukkonen A.K. Miettinen P.J. Savilahti E. Kohva E. Kariola L. Suutela M. Tarkkanen A. de Vos W.M. Raivio T. Kuitunen M. Gut microbiota develop towards an adult profile in a sex-specific manner during puberty.Sci Rep. 2021; 11: 23297Google Scholar Although prior investigations have shown that antibiotic exposure during early postnatal life can have lasting effects on hepatic metabolism and adiposity,12Cho I. Yamanishi S. Cox L. Methé B.A. Zavadil J. Li K. Gao Z. Mahana D. Raju K. Teitler I. Li H. Alekseyenko A.V. Blaser M.J. Antibiotics in early life alter the murine colonic microbiome and adiposity.Nature. 2012; 488: 621-626Google Scholar,13Cox L.M. Yamanishi S. Sohn J. Alekseyenko A.V. Leung J.M. Cho I. Kim S.G. Li H. Gao Z. Mahana D. Zárate Rodriguez J.G. Rogers A.B. Robine N. Loke P. Blaser M.J. Altering the intestinal microbiota during a critical developmental window has lasting metabolic consequences.Cell. 2014; 158: 705-721Google Scholar the impact of antibiotic exposure during adolescence is currently unclear. Recent preclinical and clinical reports support that the gut microbiota develops toward a stable, adult-like gut microbiota profile during adolescence.20Moran-Ramos S. Lopez-Contreras B.E. Villarruel-Vazquez R. Ocampo-Medina E. Macias-Kauffer L. Martinez-Medina J.N. Villamil-Ramirez H. León-Mimila P. Del Rio-Navarro B.E. Ibarra-Gonzalez I. Vela-Amieva M. Gomez-Perez F.J. Velazquez-Cruz R. Salmeron J. Reyes-Castillo Z. Aguilar-Salinas C. Canizales-Quinteros S. Environmental and intrinsic factors shaping gut microbiota composition and diversity and its relation to metabolic health in children and early adolescents: a population-based study.Gut Microbes. 2020; 11: 900-917Google Scholar,21Korpela K. Kallio S. Salonen A. Hero M. Kukkonen A.K. Miettinen P.J. Savilahti E. Kohva E. Kariola L. Suutela M. Tarkkanen A. de Vos W.M. Raivio T. Kuitunen M. Gut microbiota develop towards an adult profile in a sex-specific manner during puberty.Sci Rep. 2021; 11: 23297Google Scholar Clinical studies comparing the gut microbiota between obese and lean adolescents have demonstrated that the intestinal microbiome in obese individuals is distinct from that of lean individuals.22Carrizales-Sánchez A.K. García-Cayuela T. Hernández-Brenes C. Senés-Guerrero C. Gut microbiota associations with metabolic syndrome and relevance of its study in pediatric subjects.Gut Microbes. 2021; 13: 1960135Google Scholar, 23Del Chierico F. Abbatini F. Russo A. Quagliariello A. Reddel S. Capoccia D. Caccamo R. Ginanni Corradini S. Nobili V. De Peppo F. Dallapiccola B. Leonetti F. Silecchia G. Putignani L. Gut microbiota markers in obese adolescent and adult patients: age-dependent differential patterns.Front Microbiol. 2018; 9: 1210Google Scholar, 24Klimenko E.S. Belkova N.L. Romanitsa A.I. Pogodina A.V. Rychkova L.V. Darenskaya M.A. Differences in gut microbiota composition and predicted metabolic functions: a pilot study of adolescents with normal weight and obesity.Bull Exp Biol Med. 2022; 173: 628-632Google Scholar, 25Leong K.S.W. Jayasinghe T.N. Wilson B.C. Derraik J.G.B. Albert B.B. Chiavaroli V. Svirskis D.M. Beck K.L. Conlon C.A. Jiang Y. Schierding W. Vatanen T. Holland D.J. O'Sullivan J.M. Cutfield W.S. Effects of fecal microbiome transfer in adolescents with obesity: the gut bugs randomized controlled trial.JAMA Netw Open. 2020; 3: e2030415-eGoogle Scholar Furthermore, fecal microbiota transfer from healthy lean adolescent donors to obese adolescents reduced abdominal adiposity.25Leong K.S.W. Jayasinghe T.N. Wilson B.C. Derraik J.G.B. Albert B.B. Chiavaroli V. Svirskis D.M. Beck K.L. Conlon C.A. Jiang Y. Schierding W. Vatanen T. Holland D.J. O'Sullivan J.M. Cutfield W.S. Effects of fecal microbiome transfer in adolescents with obesity: the gut bugs randomized controlled trial.JAMA Netw Open. 2020; 3: e2030415-eGoogle Scholar Findings from these clinical investigations imply that the composition of the gut microbiota during adolescence influences host metabolism and adiposity. Adolescence is the developmental stage of life between childhood and adulthood that spans roughly from the age of 12 to 21 years.26Hardin A.P. Hackell J.M. Age limit of pediatrics.Pediatrics. 2017; 140: e20172151Google Scholar Of interest, adolescents afflicted by acne are exposed to systemic antibiotic treatment courses for extended durations. About 85% of individuals aged 12 to 24 years are afflicted by acne.27Bhate K. Williams H.C. Epidemiology of acne vulgaris.Br J Dermatol. 2013; 168: 474-485Google Scholar For acne resistant to topical therapies, the Academy of Dermatology Clinical Acne Guidelines recommends using topical therapies plus systemic antibiotics.28Zaenglein A.L. Pathy A.L. Schlosser B.J. Alikhan A. Baldwin H.E. Berson D.S. Bowe W.P. Graber E.M. Harper J.C. Kang S. Keri J.E. Leyden J.J. Reynolds R.V. Silverberg N.B. Stein Gold L.F. Tollefson M.M. Weiss J.S. Dolan N.C. Sagan A.A. Stern M. Boyer K.M. Bhushan R. Guidelines of care for the management of acne vulgaris.J Am Acad Dermatol. 2016; 74: 945-973.e33Google Scholar Adolescents and young adults prescribed systemic antibiotics for treating acne are subjected to prolonged antibiotic treatment courses. The average duration of systemic antibiotic treatment for adolescent acne ranges from 4 to 11 months.29Lee Y.H. Liu G. Thiboutot D.M. Leslie D.L. Kirby J.S. A retrospective analysis of the duration of oral antibiotic therapy for the treatment of acne among adolescents: investigating practice gaps and potential cost-savings.J Am Acad Dermatol. 2014; 71: 70-76Google Scholar, 30Nagler A.R. Milam E.C. Orlow S.J. The use of oral antibiotics before isotretinoin therapy in patients with acne.J Am Acad Dermatol. 2016; 74: 273-279Google Scholar, 31Del Rosso J.Q. Webster G.F. Rosen T. Thiboutot D. Leyden J.J. Gallo R. Walker C. Zhanel G. Eichenfield L. Status report from the Scientific Panel on Antibiotic Use in Dermatology of the American Acne and Rosacea Society: part 1: antibiotic prescribing patterns, sources of antibiotic exposure, antibiotic consumption and emergence of antibiotic resistance, impact of alterations in antibiotic prescribing, and clinical sequelae of antibiotic use.J Clin Aesthet Dermatol. 2016; 9: 18-24Google Scholar, 32Barbieri J.S. Bhate K. Hartnett K.P. Fleming-Dutra K.E. Margolis D.J. Trends in oral antibiotic prescription in dermatology, 2008 to 2016.JAMA Dermatol. 2019; 155: 290-297Google Scholar, 33Warner A.J. Hathaway-Schrader J.D. Lubker R. Davies C. Novince C.M. Tetracyclines and bone: unclear actions with potentially lasting effects.Bone. 2022; 159: 116377Google Scholar The purpose of this study was to discern the impact of prolonged antibiotic exposure during adolescence on the gut microbiota, hepatic metabolism, and adiposity. Tetracyclines (ie, minocycline and doxycycline) are the preferred systemic antibiotics for acne therapy,28Zaenglein A.L. Pathy A.L. Schlosser B.J. Alikhan A. Baldwin H.E. Berson D.S. Bowe W.P. Graber E.M. Harper J.C. Kang S. Keri J.E. Leyden J.J. Reynolds R.V. Silverberg N.B. Stein Gold L.F. Tollefson M.M. Weiss J.S. Dolan N.C. Sagan A.A. Stern M. Boyer K.M. Bhushan R. Guidelines of care for the management of acne vulgaris.J Am Acad Dermatol. 2016; 74: 945-973.e33Google Scholar,34Eichenfield D.Z. Sprague J. Eichenfield L.F. Management of acne vulgaris: a review.JAMA. 2021; 326: 2055-2067Google Scholar,35Graber E.M. Acne Vulgaris: Overview of Management. UpToDate Inc., Waltham, MA2022Google Scholar and minocycline is prescribed in roughly half of these cases.29Lee Y.H. Liu G. Thiboutot D.M. Leslie D.L. Kirby J.S. A retrospective analysis of the duration of oral antibiotic therapy for the treatment of acne among adolescents: investigating practice gaps and potential cost-savings.J Am Acad Dermatol. 2014; 71: 70-76Google Scholar,30Nagler A.R. Milam E.C. Orlow S.J. The use of oral antibiotics before isotretinoin therapy in patients with acne.J Am Acad Dermatol. 2016; 74: 273-279Google Scholar,32Barbieri J.S. Bhate K. Hartnett K.P. Fleming-Dutra K.E. Margolis D.J. Trends in oral antibiotic prescription in dermatology, 2008 to 2016.JAMA Dermatol. 2019; 155: 290-297Google Scholar,36Patel D.J. Bhatia N. Oral antibiotics for acne.Am J Clin Dermatol. 2021; 22: 193-204Google Scholar Minocycline was administered to mice during the pubertal/postpubertal growth phase to model long-term antibiotic exposure during adolescence for the clinical treatment of acne. Antibiotic exposure during the murine adolescent phase caused lasting shifts in the intestinal microbiota and a persistent dysregulation of hepatic metabolism. Dysregulated liver metabolism was associated with a sustained disruption of the intestinal farnesoid X receptor (FXR)–fibroblast growth factor 15 (FGF15) axis. The intestinal FXR-FGF15 axis is a gut-liver endocrine axis that regulates hepatic bile acid, glucose, and lipid metabolism and has been linked to changes in adiposity.37de Aguiar Vallim T.Q. Tarling E.J. Edwards P.A. Pleiotropic roles of bile acids in metabolism.Cell Metab. 2013; 17: 657-669Google Scholar, 38Chiang J.Y. Bile acid metabolism and signaling.Compr Physiol. 2013; 3: 1191-1212Google Scholar, 39Fiorucci S. Distrutti E. Bile acid-activated receptors, intestinal microbiota, and the treatment of metabolic disorders.Trends Mol Med. 2015; 21: 702-714Google Scholar, 40Wahlstrom A. Sayin S.I. Marschall H.U. Backhed F. 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To our knowledge, this is the first known study to discern the impact of prolonged antibiotic exposure during adolescence on host metabolism. Findings from this preclinical investigation underline that prolonged antibiotic courses for the clinical treatment of adolescent acne may have unintended detrimental effects on metabolism and adiposity. A retrospective, secondary data analysis of South Carolina Medicaid claims was performed to discern the prevalence of long-term tetracycline antibiotic use in adolescents diagnosed with acne for years 2019 to 2021. Individuals between the ages of 12 and 18 years were included in the analysis. Age 12 years represents the beginning of the adolescent developmental phase,26Hardin A.P. Hackell J.M. Age limit of pediatrics.Pediatrics. 2017; 140: e20172151Google Scholar and individuals who are aged <19 years and meet other requirements are eligible to receive benefits from South Carolina's Medicaid Program. Long-term tetracycline therapy was defined as a minocycline or doxycycline prescription for ≥30 days. Minocycline and doxycycline are the preferred systemic antibiotics for acne therapy.28Zaenglein A.L. Pathy A.L. Schlosser B.J. Alikhan A. Baldwin H.E. Berson D.S. Bowe W.P. Graber E.M. Harper J.C. Kang S. Keri J.E. Leyden J.J. Reynolds R.V. Silverberg N.B. Stein Gold L.F. Tollefson M.M. Weiss J.S. Dolan N.C. Sagan A.A. Stern M. Boyer K.M. Bhushan R. Guidelines of care for the management of acne vulgaris.J Am Acad Dermatol. 2016; 74: 945-973.e33Google Scholar,34Eichenfield D.Z. Sprague J. Eichenfield L.F. Management of acne vulgaris: a review.JAMA. 2021; 326: 2055-2067Google Scholar,35Graber E.M. Acne Vulgaris: Overview of Management. UpToDate Inc., Waltham, MA2022Google Scholar Supplemental Figure S1 summarizes the data management process. Five-week–old male C57BL/6T specific pathogen-free (SPF) mice were purchased from Taconic Biosciences (Rensselaer, NY). Animals were housed in ventilated cages in the same SPF vivarium, at the Medical University of South Carolina. Room temperature/humidity were maintained within the advised ranges per the NIH Guide for the Care and Use of Laboratory Animals.51Committee for the Update of the Guide for the Care and Use of Laboratory Animals; National Research CouncilGuide for the Care and Use of Laboratory Animals.Eighth Edition. National Academies Press, Washington, DC2011Google Scholar Animals were maintained on a 12:12-hour light/dark schedule and received an autoclaved NIH-31M diet (Zeigler, Gardners, PA). SPF mice were acclimated to housing conditions for 1 week before initiating vehicle-control or minocycline treatment at the age of 6 weeks. Animals were administered sterile-filtered 100 mg/L minocycline hydrochloride or vehicle-control drinking water from the age of 6 to 12 weeks. Cages were changed every 2 weeks. Experimental groups were euthanized at the ages of 12 and 18 weeks to assess immediate and sustained antibiotic treatment effects. The 100 mg/L minocycline hydrochloride drinking water supported administering a 25 mg/kg murine daily dose, which is equivalent to a clinical 2.0 mg/kg daily dose.28Zaenglein A.L. Pathy A.L. Schlosser B.J. Alikhan A. Baldwin H.E. Berson D.S. Bowe W.P. Graber E.M. Harper J.C. Kang S. Keri J.E. Leyden J.J. Reynolds R.V. Silverberg N.B. Stein Gold L.F. Tollefson M.M. Weiss J.S. Dolan N.C. Sagan A.A. Stern M. Boyer K.M. Bhushan R. Guidelines of care for the management of acne vulgaris.J Am Acad Dermatol. 2016; 74: 945-973.e33Google Scholar,52Bachmanov A.A. Reed D.R. Beauchamp G.K. Tordoff M.G. Food intake, water intake, and drinking spout side preference of 28 mouse strains.Behav Genet. 2002; 32: 435-443Google Scholar,53Nair A.B. Jacob S. A simple practice guide for dose conversion between animals and human.J Basic Clin Pharm. 2016; 7: 27-31Google Scholar Prior reports have shown that antibiotic delivery via drinking water, injection, and gavage has similar effects on the richness and abundance of bacterial communities in the gut microbiota.54Tirelle P. Breton J. Riou G. Déchelotte P. Coëffier M. Ribet D. Comparison of different modes of antibiotic delivery on gut microbiota depletion efficiency and body composition in mouse.BMC Microbiol. 2020; 20: 340Google Scholar,55Kelly S.A. Nzakizwanayo J. Rodgers A.M. Zhao L. Weiser R. Tekko I.A. McCarthy H.O. Ingram R.J. Jones B.V. Donnelly R.F. Gilmore B.F. Antibiotic therapy and the gut microbiome: investigating the effect of delivery route on gut pathogens.ACS Infect Dis. 2021; 7: 1283-1296Google Scholar Thus, minocycline hydrochloride was administered through the drinking water to limit distress and harm to animals. Study was approved by the Medical University of South Carolina Institutional Animal Care and Use Committee and conducted in accordance with the NIH Guide for Care and Use of Laboratory Animals and reported by Animal Research: Reporting of In Vivo Experiments (ARRIVE) guidelines (https://arriveguidelines.org/arrive-guidelines, last accessed February 16, 2023).56Percie du Sert N. Ahluwalia A. Alam S. Avey M.T. Baker M. Browne W.J. Clark A. Cuthill I.C. Dirnagl U. Emerson M. Garner P. Holgate S.T. Howells D.W. Hurst V. Karp N.A. Lazic S.E. Lidster K. MacCallum C.J. Macleod M. Pearl E.J. Petersen O.H. Rawle F. Reynolds P. Rooney K. Sena E.S. Silberberg S.D. Steckler T. Würbel H. Reporting animal research: explanation and elaboration for the ARRIVE guidelines 2.0.PLoS Biol. 2020; 18: e3000411Google Scholar The retrospective analysis of South Carolina Medicaid claims was deemed exempt and approved by the Medical University of South Carolina Institutional Review Board. Genomic DNA was isolated from colonic contents using the DNeasy PowerSoil Pro Kit (Qiagen, Hilden, Germany). Total DNA was quantified via NanoDrop 1000 (Thermo Fisher Scientific, Waltham, MA). Library preparation and sequencing was performed by the North Carolina State University Genomics Sciences Laboratory. Bacterial 16S rDNA V3 and V4 variable regions were amplified by PCR. Illumina (San Diego, CA) sequencing adapters were added during a second PCR amplification step following cleanup. Specimens were collected, pooled, and sequenced on Illumina MiSeq v3 Reagent Kit for 2 × 300 cycles. FASTQ files were filtered and processed using the DADA2 pipeline version 1.24 in the R statistical pro" @default.
• W4323657859 created "2023-03-10" @default.
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• W4323657859 date "2023-06-01" @default.
• W4323657859 modified "2023-10-17" @default.
• W4323657859 title "Prolonged Antibiotic Exposure during Adolescence Dysregulates Liver Metabolism and Promotes Adiposity in Mice" @default.
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